BIOMD0000000395
type: SBMLModel
reaction: 119551
species: 119230
species: 119076
species: 118940
parameter: 119674
reaction: 119575
occurs in: http://identifiers.org/taxonomy/40674
species: 119134
species: 118959
parameter: 119666
parameter: 119656
parameter: 119663
parameter: 119657
compartment: 118862
is version of: GO:0007224
species: 119173
species: 118998
modified:
  W3 CDTF: Fri Apr 20 20:39:57 BST 2012
name: Sivakumar2011_HedgehogSignalingPathway
parameter: 119676
parameter: 119677
parameter: 119665
reaction: 119481
parameter: 119672
length unit: length
species: 119289
parameter: 119673
substance units: 142808
parameter: 119661
parameter: 119662
parameter: 119652
species: 119153
species: 119192
parameter: 119669
species: 119096
compartment: 118861
is described by: http://identifiers.org/pubmed/21978399
reaction: 119503
species: 119308
compartment: 118900
creator:
  ORG:
    orgname: Rajiv Gandhi Centre for Biotechnology
  n:
    given: KC
    family: Sivakumar
parameter: 119675
species: 119346
species: 119017
species: 118920
parameter: 119670
parameter: 119664
parameter: 119671
time units: 949038
parameter: 119658
parameter: 119659
reaction: 119458
reaction: 119527
area units: 498119
reaction: 119366
is: MODEL1101270001
species: 119114
volume units: 142784
species: 118978
species: 119036
species: 119211
reaction: 119389
species: 119250
species: 119057
parameter: 119651
notes: This model is from the article: A systems biology approach to model neural stem cell regulation by notch, shh, wnt, and EGF signaling pathways. Sivakumar KC, Dhanesh SB, Shobana S, James J, Mundayoor S. OMICS 2011 Oct;15(10):729-37. 21978399 , Abstract: The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have long been known to in fluence cell fate specification in the developing nervous system. Here we attempt ed to evaluate the contemporary knowledge about neural stem cell differentiation promoted by various drug-based regulations through a systems biology approach. Ou r model showed the phenomenon of DAPT-mediated antagonism of Enhancer of split [E (spl)] genes and enhancement of Shh target genes by a SAG agonist that were effec tively demonstrated computationally and were consistent with experimental studies . However, in the case of model simulation of Wnt and EGF pathways, the model net work did not supply any concurrent results with experimental data despite the fac t that drugs were added at the appropriate positions. This paves insight into the potential of crosstalks between pathways considered in our study. Therefore, we manually developed a map of signaling crosstalk, which included the species conne cted by representatives from Notch, Shh, Wnt, and EGF pathways and highlighted th e regulation of a single target gene, Hes-1, based on drug-induced simulations. T hese simulations provided results that matched with experimental studies. Therefo re, these signaling crosstalk models complement as a tool toward the discovery of novel regulatory processes involved in neural stem cell maintenance, proliferati on, and differentiation during mammalian central nervous system development. To o ur knowledge, this is the first report of a simple crosstalk map that highlights the differential regulation of neural stem cell differentiation and underscores t he flow of positive and negative regulatory signals modulated by drugs. Note: This is the current model for the…
parameter: 119667
parameter: 119668
reaction: 119433
curated: true
species: 119327
species: 119269
parameter: 119653
parameter: 119660
occurs in: CL:0000047
reaction: 119619
reaction: 119598
reaction: 119410
compartment: 118881

119551
type: Reaction
notes: reversible simple convenience kinetics
modifier: 196492
fast: false
reactant: 196456
kinetic law: 196504
product: 196480
product: 196468
reversible: true

119036
type: Species
boundary condition: false
name: Complex_br_(Patched/Hedgehog)
constant: false
initial concentration: NaN
is version of: GO:0043234
notes: Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05221 Heterodimer Member Info: Hedgehog#PROTEIN#Hedgehog#P00688#Hh|Shh|Sonic hedgehog#;Patched#PROTEIN#Patched#P00689#Ptc|Ptc1#
initial amount: 0.0
has only substance units: false
in compartment: 118862

118862
type: Compartment
constant: true
size: 1.0
spatial dimensions: 3.0
name: Receiving cell

196456
type: SpeciesReference
stoichiometry: 1.0
species: 119308

119308
type: Species
is version of: GO:0043234
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 118881
name: Complex_br_(Costal2/Fused/../microtubule)

118881
type: Compartment
constant: true
size: 1.0
spatial dimensions: 3.0
name: lipid raft

196480
type: SpeciesReference
stoichiometry: 1.0
species: 119327

119327
type: Species
is version of: GO:0043234
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 118881
name: Complex_br_(Su(fu)/Fused/../_br_Smoothened)

196468
type: SpeciesReference
stoichiometry: 1.0
species: 119134

119134
type: Species
initial concentration: NaN
has only substance units: false
name: Microtubule
boundary condition: false
is: GO:0005874
notes: Long Name: Microtubule Synonym: Synonym not specified Accession: P00696
initial amount: 0.0
in compartment: 118862
constant: false

119230
type: Species
is version of: GO:0043234
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 3.0
in compartment: 118862
name: complex

119076
type: Species
is version of: GO:0043234
boundary condition: false
notes: Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05228 Heterodimer Member Info: Smoothened#PROTEIN#Smoothened#P00685#Smo#;Fused#PROTEIN#Fused#P00686#Fu#;Costal2#PROTEIN#Costal2#P00698#Cos-2|Cos2|Costal-2#
name: Complex_br_(Costal2/Smoothened/_br_Fused)
constant: false
in compartment: 118862
initial concentration: NaN
has only substance units: false
initial amount: 0.0

118940
type: Species
initial concentration: NaN
initial amount: 0.0
is version of: CHEBI:16761
notes: Long Name: ADP Synonym: Synonym not specified Accession: S01693
has only substance units: false
constant: false
boundary condition: false
in compartment: 118862
name: ADP

119674
type: Parameter
constant: true
value: 0.89

119575
type: Reaction
kinetic law: 196552
product: 196540
reactant: 196528
reactant: 196516
notes: mass action rate law for second order forward, first order reverse, reversible reactions, two reactants, continuous scheme
fast: false
reversible: true

196540
type: SpeciesReference
stoichiometry: 1.0
species: 119289

119289
type: Species
is version of: GO:0043234
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 118900
name: Complex_br_(CBP/Cubitus)

118900
type: Compartment
constant: true
size: 1.0
spatial dimensions: 3.0
name: nucleus

196528
type: SpeciesReference
stoichiometry: 1.0
species: 119114

119114
type: Species
in compartment: 118900
is version of: Q92793
constant: false
notes: Long Name: CBP Synonym: CREB binding protein,p300 Accession: P00691
initial concentration: NaN
boundary condition: false
name: CBP
has only substance units: false
initial amount: 2.0

196516
type: SpeciesReference
stoichiometry: 1.0
species: 119153

119153
type: Species
constant: false
initial amount: 0.0
has only substance units: false
notes: Long Name: Cubitus interruptus Synonym: Ci,CiFL,Gli1,Gli2,Gli3 Accession: P00690
name: Cubitus_space_interruptus
boundary condition: false
in compartment: 118900
initial concentration: NaN
is homolog to: B4NUI3

118959
type: Species
boundary condition: false
notes: Long Name: Patched Synonym: Ptc,Ptc1 Accession: P00689
name: Patched
is version of: Q13635
initial concentration: NaN
in compartment: 118862
initial amount: 5.0
has only substance units: false
constant: false

119666
type: Parameter
constant: true
value: 1.67

119656
type: Parameter
constant: true
value: 1.03

119663
type: Parameter
constant: true
value: 1.23

119657
type: Parameter
constant: true
value: 1.75

119173
type: Species
initial concentration: NaN
initial amount: 2.5
is version of: GO:0043234
in compartment: 118900
has only substance units: false
name: Complex_br_(Cubitus_space_interruptus_space_repressor/Su(fu))
constant: false
boundary condition: false
notes: Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05220 Heterodimer Member Info: Cubitus interruptus repressor#PROTEIN#Cubitus interruptus repressor#P00687#CiR#;Su(fu)#PROTEIN#Su(fu)#P00699#Suppressor of Fused#

118998
type: Species
has only substance units: false
in compartment: 118900
initial amount: 2.5
notes: Long Name: Sap18 Synonym: Sin3-associated polypeptide 18 Accession: P00697
boundary condition: false
name: Sap18
constant: false
initial concentration: NaN
is homolog to: Q3MHS8

119676
type: Parameter
constant: true
value: 1.0

119677
type: Parameter
constant: true
value: 1.0

119665
type: Parameter
constant: true
value: 0.6

119481
type: Reaction
kinetic law: 196312
modifier: 196300
product: 196288
reactant: 196276
notes: kinetics of non-modulated unireactant enzymes
fast: false
reversible: true

196288
type: SpeciesReference
stoichiometry: 1.0
species: 119153

196276
type: SpeciesReference
stoichiometry: 1.0
species: 119153

119672
type: Parameter
constant: true
value: 1.56

119673
type: Parameter
constant: true
value: 1.53

119661
type: Parameter
constant: true
value: 1.33

119662
type: Parameter
constant: true
value: 0.61

119652
type: Parameter
constant: true
value: 1.122

119192
type: Species
has only substance units: false
initial amount: 0.0
boundary condition: false
initial concentration: NaN
notes: Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05217 Heterodimer Member Info: Cubitus interruptus repressor#PROTEIN#Cubitus interruptus repressor#P00687#CiR#;Sap18#PROTEIN#Sap18#P00697#Sin3-associated polypeptide 18#;Su(fu)#PROTEIN#Su(fu)#P00699#Suppressor of Fused#
in compartment: 118900
is version of: GO:0043234
name: Complex_br_(Sap18/Su(fu)/_br_Cubitus_space_interruptus_space_repressor)
constant: false

119669
type: Parameter
constant: true
value: 1.62

119096
type: Species
name: Complex_br_(Costal2/Fused/_br_Smoothened)
initial amount: 0.0
notes: Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05229 Heterodimer Member Info: Smoothened#PROTEIN#Smoothened#P00685#Smo#;Fused#PROTEIN#Fused#P00686#Fu#;Costal2#PROTEIN#Costal2#P00698#Cos-2|Cos2|Costal-2#
constant: false
boundary condition: false
is version of: GO:0043234
in compartment: 118881
has only substance units: false
initial concentration: NaN

118861
type: Compartment
constant: true
size: 1.0
spatial dimensions: 3.0

119503
type: Reaction
kinetic law: 196372
product: 196348
reversible: false
notes: mass action rate law for second order irreversible reactions, two reactants, continuous scheme
reactant: 196324
reactant: 196336
fast: false
modifier: 196360

196348
type: SpeciesReference
stoichiometry: 1.0
species: 119308

196324
type: SpeciesReference
stoichiometry: 1.0
species: 119211

119211
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 3.0
in compartment: 118862
name: smoothened

196336
type: SpeciesReference
stoichiometry: 1.0
species: 119230

119269
type: Species
is version of: P10523
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.5
in compartment: 118862
name: sag

119675
type: Parameter
constant: true
value: 1.0

119346
type: Species
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 118862
name: Complex_br_(Su(fu)/Cubitus)

119017
type: Species
boundary condition: false
constant: false
notes: Long Name: Hedgehog Synonym: Hh,Shh,Sonic hedgehog Accession: P00688
name: Hedgehog
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 118861
is version of: Q15465

118920
type: Species
constant: false
is version of: CHEBI:15422
notes: Long Name: ATP Synonym: Synonym not specified Accession: S01691
initial concentration: NaN
initial amount: 2.0
in compartment: 118862
name: ATP
has only substance units: false
boundary condition: false

119670
type: Parameter
constant: true
value: 1.28

119664
type: Parameter
constant: true
value: 0.46

119671
type: Parameter
constant: true
value: 0.71

119658
type: Parameter
constant: true
value: 0.215

119659
type: Parameter
constant: true
value: 1.27

119458
type: Reaction
kinetic law: 196264
product: 196252
reactant: 196240
reactant: 196228
notes: mass action rate law for second order forward, first order reverse, reversible reactions, two reactants, continuous scheme
fast: false
reversible: true

196252
type: SpeciesReference
stoichiometry: 1.0
species: 119192

196240
type: SpeciesReference
stoichiometry: 1.0
species: 119173

196228
type: SpeciesReference
stoichiometry: 1.0
species: 118998

119527
type: Reaction
notes: reversible rapid-equilibrium random order ternary-complex mechanism with two products
reactant: 196384
product: 196408
fast: false
reversible: true
product: 196420
modifier: 196432
kinetic law: 196444
reactant: 196396

196384
type: SpeciesReference
stoichiometry: 1.0
species: 119057

119057
type: Species
notes: Long Name: Long Name: Smoothened Synonym: Synonym not specified Accession: U05226 Heterodimer Member Info: Smoothened#PROTEIN#Smoothened#P00685#Smo#;Fused#PROTEIN#Fused#P00686#Fu#;Costal2#PROTEIN#Costal2#P00698#Cos-2|Cos2|Costal-2#
is version of: GO:0043234
boundary condition: false
initial amount: 0.0
in compartment: 118862
constant: false
initial concentration: NaN
has only substance units: false
name: Complex_br_(Costal2/Fused/_br_Smoothened)

196408
type: SpeciesReference
stoichiometry: 1.0
species: 119076

196420
type: SpeciesReference
stoichiometry: 1.0
species: 118940

196396
type: SpeciesReference
stoichiometry: 1.0
species: 118920

119366
type: Reaction
kinetic law: 196084
product: 196072
reactant: 196060
fast: false
reversible: false

196072
type: SpeciesReference
stoichiometry: 1.0
species: 118978

118978
type: Species
initial concentration: NaN
is described by: GO:0007228
name: Hedgehog target gene
constant: false
has only substance units: false
initial amount: 0.0
boundary condition: false
notes: Long Name: e.g., ptc Synonym: Synonym not specified Accession: G01526
in compartment: 118900

196060
type: SpeciesReference
stoichiometry: 1.0
species: 119192

119389
type: Reaction
kinetic law: 196120
product: 196108
reactant: 196096
fast: false
reversible: false

196108
type: SpeciesReference
stoichiometry: 1.0
species: 118978

196096
type: SpeciesReference
stoichiometry: 1.0
species: 119289

119250
type: Species
is version of: GO:0005874
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 118862
name: MIcrotubule

119651
type: Parameter
constant: true
value: 1.13

119667
type: Parameter
constant: true
value: 1.29

119668
type: Parameter
constant: true
value: 0.79

119433
type: Reaction
kinetic law: 196216
modifier: 196204
product: 196192
reactant: 196180
notes: kinetics of non-modulated unireactant enzymes
fast: false
reversible: true

196192
type: SpeciesReference
stoichiometry: 1.0
species: 119057

196180
type: SpeciesReference
stoichiometry: 1.0
species: 119096

119653
type: Parameter
constant: true
value: 1.146

119660
type: Parameter
constant: true
value: 0.73

119619
type: Reaction
kinetic law: 196636
product: 196624
product: 196612
reactant: 196600
notes: mass action rate law for first order forward, second order reverse, reversible reactions, two products, continuous scheme
fast: false
reversible: true

196624
type: SpeciesReference
stoichiometry: 1.0
species: 119096

196612
type: SpeciesReference
stoichiometry: 1.0
species: 119346

196600
type: SpeciesReference
stoichiometry: 1.0
species: 119327

119598
type: Reaction
kinetic law: 196588
product: 196576
reactant: 196564
notes: mass action rate law for first order forward, first order reverse, reversible reactions, continuous scheme
fast: false
reversible: true

196576
type: SpeciesReference
stoichiometry: 1.0
species: 119153

196564
type: SpeciesReference
stoichiometry: 1.0
species: 119346

119410
type: Reaction
kinetic law: 196168
product: 196156
reactant: 196144
reactant: 196132
notes: mass action rate law for second order forward, first order reverse, reversible reactions, two reactants, continuous scheme
fast: false
reversible: true

196156
type: SpeciesReference
stoichiometry: 1.0
species: 119036

196144
type: SpeciesReference
stoichiometry: 1.0
species: 118959

196132
type: SpeciesReference
stoichiometry: 1.0
species: 119017

W3 CDTF: Wed Nov 02 14:45:21 GMT 2011

ORG:
  orgname: EMBL-EBI
n:
  given: Vijayalakshmi
  family: Chelliah